Triethylamine → N-[5-(2,3-Difluorophenyl)-1-(2-methoxyethyl)-2-oxopiperidin-3-yl]-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxamide

HRID 493687

Reaction equation

HRID 493687 reaction equation
C(N(CC)CC)C.[NH2:8][CH:9]1[CH2:14][CH:13]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([F:21])[C:16]=2[F:22])[CH2:12][N:11]([CH2:23][CH2:24][O:25][CH3:26])[C:10]1=[O:27].C1C([N+]([O-])=O)=CC=C([Cl-][C:38]([O-])=[O:39])C=1.Cl.Cl.[O:43]=[C:44]1[NH:52][C:47]2=[N:48][CH:49]=[CH:50][CH:51]=[C:46]2[N:45]1[CH:53]1[CH2:58][CH2:57][NH:56][CH2:55][CH2:54]1.C(=O)(O)[O-].[Na+]>O1CCCC1>[F:22][C:16]1[C:17]([F:21])=[CH:18][CH:19]=[CH:20][C:15]=1[CH:13]1[CH2:12][N:11]([CH2:23][CH2:24][O:25][CH3:26])[C:10](=[O:27])[CH:9]([NH:8][C:38]([N:56]2[CH2:57][CH2:58][CH:53]([N:45]3[C:46]4[C:47](=[N:48][CH:49]=[CH:50][CH:51]=4)[NH:52][C:44]3=[O:43])[CH2:54][CH2:55]2)=[O:39])[CH2:14]1

Participants

6

Reactant 4

HCID 8471Triethylamine2×HCID 516892Sodium BicarbonateHCID 222931811-(piperidin-4-yl)-1H,2H,3H-imidazo[4,5-b]pyridin-2-one dihydrochlorideHCID 222931943-Amino-5-(2,3-difluorophenyl)-1-(2-methoxyethyl)piperidin-2-one

Product 1

HCID 22293309N-[5-(2,3-Difluorophenyl)-1-(2-methoxyethyl)-2-oxopiperidin-3-yl]-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxamideYield 42.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Triethylamine (83 μL, 0.598 mmol) was added to a solution of 3-amino-5-(2,3-difluorophenyl)-1-(2-methoxyethyl)piperidin-2-one (170 mg, 0.598 mmol) and 4-nitrophenylchloroformate (121 mg, 0.598 mmol) in tetrahydrofuran (4 mL) at 0° C. After 1 h, 2-oxo-1-(4-piperidinyl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine dihydrochloride (174 mg, 0.651 mmol), triethylamine (249 μL, 1.794 mmol) were added and the mixture allowed to warm to ambient temperature. After 18 h, saturated aqueous sodium bicarbonate was added and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium bicarbonate (3×), saturated brine, dried over sodium sulfate, filtered and concentrated. Purification by silica gel chromatography [100% dichloromethane→95% dichloromethane/5% (10% ammonium hydroxide/methanol)] gave the title compound (0.135 g). MS 529.2353 (M+1). 1H NMR (500 MHz, CDCl3) δ 8.03 (dd, J=5.3, 1.1 Hz, 1H), 7.38 (dd, J=7.8, 1.2 Hz, 1H), 7.11-7.03 (m, 2H), 7.01-6.96 (m, 2H), 5.82 (d, J=3.4 Hz, 1H), 4.58-4.53 (m, 1H), 4.34-4.30 (m, 1H), 4.23 (d, J=6.6 Hz, 2H), 3.71-3.62 (m, 3H), 3.60-3.53 (m, 3H), 3.52-3.46 (m, 1H), 3.33 (s, 3H), 2.96 (dd, J=23.4, 10.5 Hz, 2H), 2.80-2.78 (m, 1H), 2.28-2.21 (m, 2H), 1.90 (dd, J=10.5, 2.0 Hz, 2H).

Workup

  1. waitAfter 18 h
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe organic layer was washed with saturated aqueous sodium bicarbonate (3×), saturated brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification by silica gel chromatography [100% dichloromethane→95% dichloromethane/5% (10% ammonium hydroxide/methanol)]

Sources & evidence

ORD record
ord-fd8ce231d3f04725a82b12ea887d3c34
Source dataset
uspto-grants-2009_05
Patent number
US07534784B2

Linked notes

Loading…